TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20442	61549;61550;61551	chr2:178590401;178590400;178590399	chr2:179455128;179455127;179455126
N2AB	18801	56626;56627;56628	chr2:178590401;178590400;178590399	chr2:179455128;179455127;179455126
N2A	17874	53845;53846;53847	chr2:178590401;178590400;178590399	chr2:179455128;179455127;179455126
N2B	11377	34354;34355;34356	chr2:178590401;178590400;178590399	chr2:179455128;179455127;179455126
Novex-1	11502	34729;34730;34731	chr2:178590401;178590400;178590399	chr2:179455128;179455127;179455126
Novex-2	11569	34930;34931;34932	chr2:178590401;178590400;178590399	chr2:179455128;179455127;179455126
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-36
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.3359
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/Q	rs751412533	None	0.999	N	0.563	0.316	0.475112344478	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93874E-04	None	0	0	0	0	0
E/Q	rs751412533	None	0.999	N	0.563	0.316	0.475112344478	gnomAD-4.0.0	6.57082E-06	None	None	None	None	N	None	0	0	None	0	1.94326E-04	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.2557	likely_benign	0.2137	benign	-0.921	Destabilizing	0.4	N	0.301	neutral	D	0.523311405	None	None	N
E/C	0.8964	likely_pathogenic	0.8803	pathogenic	-0.478	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.2477	likely_benign	0.248	benign	-0.859	Destabilizing	0.99	D	0.483	neutral	N	0.518654947	None	None	N
E/F	0.8833	likely_pathogenic	0.8543	pathogenic	-0.167	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
E/G	0.4155	ambiguous	0.3264	benign	-1.288	Destabilizing	0.98	D	0.641	neutral	N	0.484032218	None	None	N
E/H	0.6519	likely_pathogenic	0.6061	pathogenic	-0.324	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	N
E/I	0.4556	ambiguous	0.4283	ambiguous	0.086	Stabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
E/K	0.3096	likely_benign	0.2301	benign	-0.442	Destabilizing	0.99	D	0.504	neutral	N	0.511419543	None	None	N
E/L	0.5947	likely_pathogenic	0.5494	ambiguous	0.086	Stabilizing	0.985	D	0.686	prob.neutral	None	None	None	None	N
E/M	0.6188	likely_pathogenic	0.5793	pathogenic	0.452	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/N	0.4187	ambiguous	0.4076	ambiguous	-1.025	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
E/P	0.7065	likely_pathogenic	0.6284	pathogenic	-0.229	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
E/Q	0.2154	likely_benign	0.19	benign	-0.881	Destabilizing	0.999	D	0.563	neutral	N	0.5113049	None	None	N
E/R	0.476	ambiguous	0.3714	ambiguous	-0.114	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
E/S	0.3287	likely_benign	0.299	benign	-1.33	Destabilizing	0.971	D	0.515	neutral	None	None	None	None	N
E/T	0.2746	likely_benign	0.2522	benign	-1.015	Destabilizing	0.469	N	0.287	neutral	None	None	None	None	N
E/V	0.2924	likely_benign	0.2661	benign	-0.229	Destabilizing	0.98	D	0.67	neutral	N	0.470131471	None	None	N
E/W	0.9604	likely_pathogenic	0.9437	pathogenic	0.186	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/Y	0.7944	likely_pathogenic	0.7565	pathogenic	0.119	Stabilizing	0.999	D	0.787	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.